The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes

Autores
dos Santos Pereira, Maurício; Maitan Santos, Bruna; Gimenez, Rocio Aldana; Silveira Guimaraes, Francisco; Raisman Vozari, Rita; Del Bel, Elaine; Michel, Patrick Pierre
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To study the anti-inflammatory potential of the two synthetic cannabinoids 4′-F-CBD and HU-910, we used post-natal brain cultures of mouse microglial cells and astrocytes activated by reference inflammogens. We found that 4′-F-CBD and HU-910 efficiently curtailed the release of TNF-α, IL-6, and IL-1β in microglia and astrocytes activated by the bacterial Toll-Like Receptor (TLR)4 ligand LPS. Upon LPS challenge, 4′-F-CBD and HU-910 also prevented the activation of phenotypic activation markers specific to microglia and astrocytes, that is, Iba-1 and GFAP, respectively. In microglial cells, the two test compounds also efficiently restrained LPS-stimulated release of glutamate, a non-cytokine inflammation marker for these cells. The immunosuppressive effects of the two cannabinoid compounds were concentration-dependent and observable between 1 and 10 μM. These effects were not dependent on cannabinoid or cannabinoid-like receptors. Both 4′-F-CBD and HU-910 were also capable of restraining the inflammogenic activity of Pam3CSK4, a lipopeptide that activates TLR2, and of BzATP, a prototypic agonist of P2X7 purinergic receptors, suggesting that these two cannabinoids could exert immunosuppressive effects against a variety of inflammatory stimuli. Using LPS-stimulated microglia and astrocytes, we established that the immunosuppressive action of 4′-F-CBD and HU-910 resulted from the inhibition of ROS produced by NADPH oxidase and subsequent repression of NF-κB-dependent signaling events. Our results suggest that 4′-F-CBD and HU-910 may have therapeutic utility in pathological conditions where neuroinflammatory processes are prominent.
Fil: dos Santos Pereira, Maurício. Universidade de Sao Paulo; Brasil. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia
Fil: Maitan Santos, Bruna. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia. Universidade de Sao Paulo; Brasil
Fil: Gimenez, Rocio Aldana. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Silveira Guimaraes, Francisco. Universidade de Sao Paulo; Brasil
Fil: Raisman Vozari, Rita. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia
Fil: Del Bel, Elaine. Universidade de Sao Paulo; Brasil
Fil: Michel, Patrick Pierre. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia
Materia
ASTROCYTES
MICROGLIA
NEUROINFLAMMATION
OXIDATIVE STRESS
SYNTHETIC CANNABINOIDS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/265488
Acceder
id CONICETDig_6185a3bb425e5d134e6eac75b44cae5a
oai_identifier_str oai:ri.conicet.gov.ar:11336/265488
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytesdos Santos Pereira, MaurícioMaitan Santos, BrunaGimenez, Rocio AldanaSilveira Guimaraes, FranciscoRaisman Vozari, RitaDel Bel, ElaineMichel, Patrick PierreASTROCYTESMICROGLIANEUROINFLAMMATIONOXIDATIVE STRESSSYNTHETIC CANNABINOIDShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1To study the anti-inflammatory potential of the two synthetic cannabinoids 4′-F-CBD and HU-910, we used post-natal brain cultures of mouse microglial cells and astrocytes activated by reference inflammogens. We found that 4′-F-CBD and HU-910 efficiently curtailed the release of TNF-α, IL-6, and IL-1β in microglia and astrocytes activated by the bacterial Toll-Like Receptor (TLR)4 ligand LPS. Upon LPS challenge, 4′-F-CBD and HU-910 also prevented the activation of phenotypic activation markers specific to microglia and astrocytes, that is, Iba-1 and GFAP, respectively. In microglial cells, the two test compounds also efficiently restrained LPS-stimulated release of glutamate, a non-cytokine inflammation marker for these cells. The immunosuppressive effects of the two cannabinoid compounds were concentration-dependent and observable between 1 and 10 μM. These effects were not dependent on cannabinoid or cannabinoid-like receptors. Both 4′-F-CBD and HU-910 were also capable of restraining the inflammogenic activity of Pam3CSK4, a lipopeptide that activates TLR2, and of BzATP, a prototypic agonist of P2X7 purinergic receptors, suggesting that these two cannabinoids could exert immunosuppressive effects against a variety of inflammatory stimuli. Using LPS-stimulated microglia and astrocytes, we established that the immunosuppressive action of 4′-F-CBD and HU-910 resulted from the inhibition of ROS produced by NADPH oxidase and subsequent repression of NF-κB-dependent signaling events. Our results suggest that 4′-F-CBD and HU-910 may have therapeutic utility in pathological conditions where neuroinflammatory processes are prominent.Fil: dos Santos Pereira, Maurício. Universidade de Sao Paulo; Brasil. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; FranciaFil: Maitan Santos, Bruna. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia. Universidade de Sao Paulo; BrasilFil: Gimenez, Rocio Aldana. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Silveira Guimaraes, Francisco. Universidade de Sao Paulo; BrasilFil: Raisman Vozari, Rita. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; FranciaFil: Del Bel, Elaine. Universidade de Sao Paulo; BrasilFil: Michel, Patrick Pierre. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; FranciaWiley-liss, div John Wiley & Sons Inc.2023-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/265488dos Santos Pereira, Maurício; Maitan Santos, Bruna; Gimenez, Rocio Aldana; Silveira Guimaraes, Francisco; Raisman Vozari, Rita; et al.; The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes; Wiley-liss, div John Wiley & Sons Inc.; Glia; 72; 3; 11-2023; 529-5450894-1491CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/glia.24489info:eu-repo/semantics/altIdentifier/doi/10.1002/glia.24489info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:43:17Zoai:ri.conicet.gov.ar:11336/265488instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:43:17.502CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes
title The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes
spellingShingle The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes
dos Santos Pereira, Maurício
ASTROCYTES
MICROGLIA
NEUROINFLAMMATION
OXIDATIVE STRESS
SYNTHETIC CANNABINOIDS
title_short The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes
title_full The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes
title_fullStr The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes
title_full_unstemmed The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes
title_sort The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes
dc.creator.none.fl_str_mv dos Santos Pereira, Maurício
Maitan Santos, Bruna
Gimenez, Rocio Aldana
Silveira Guimaraes, Francisco
Raisman Vozari, Rita
Del Bel, Elaine
Michel, Patrick Pierre
author dos Santos Pereira, Maurício
author_facet dos Santos Pereira, Maurício
Maitan Santos, Bruna
Gimenez, Rocio Aldana
Silveira Guimaraes, Francisco
Raisman Vozari, Rita
Del Bel, Elaine
Michel, Patrick Pierre
author_role author
author2 Maitan Santos, Bruna
Gimenez, Rocio Aldana
Silveira Guimaraes, Francisco
Raisman Vozari, Rita
Del Bel, Elaine
Michel, Patrick Pierre
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ASTROCYTES
MICROGLIA
NEUROINFLAMMATION
OXIDATIVE STRESS
SYNTHETIC CANNABINOIDS
topic ASTROCYTES
MICROGLIA
NEUROINFLAMMATION
OXIDATIVE STRESS
SYNTHETIC CANNABINOIDS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv To study the anti-inflammatory potential of the two synthetic cannabinoids 4′-F-CBD and HU-910, we used post-natal brain cultures of mouse microglial cells and astrocytes activated by reference inflammogens. We found that 4′-F-CBD and HU-910 efficiently curtailed the release of TNF-α, IL-6, and IL-1β in microglia and astrocytes activated by the bacterial Toll-Like Receptor (TLR)4 ligand LPS. Upon LPS challenge, 4′-F-CBD and HU-910 also prevented the activation of phenotypic activation markers specific to microglia and astrocytes, that is, Iba-1 and GFAP, respectively. In microglial cells, the two test compounds also efficiently restrained LPS-stimulated release of glutamate, a non-cytokine inflammation marker for these cells. The immunosuppressive effects of the two cannabinoid compounds were concentration-dependent and observable between 1 and 10 μM. These effects were not dependent on cannabinoid or cannabinoid-like receptors. Both 4′-F-CBD and HU-910 were also capable of restraining the inflammogenic activity of Pam3CSK4, a lipopeptide that activates TLR2, and of BzATP, a prototypic agonist of P2X7 purinergic receptors, suggesting that these two cannabinoids could exert immunosuppressive effects against a variety of inflammatory stimuli. Using LPS-stimulated microglia and astrocytes, we established that the immunosuppressive action of 4′-F-CBD and HU-910 resulted from the inhibition of ROS produced by NADPH oxidase and subsequent repression of NF-κB-dependent signaling events. Our results suggest that 4′-F-CBD and HU-910 may have therapeutic utility in pathological conditions where neuroinflammatory processes are prominent.
Fil: dos Santos Pereira, Maurício. Universidade de Sao Paulo; Brasil. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia
Fil: Maitan Santos, Bruna. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia. Universidade de Sao Paulo; Brasil
Fil: Gimenez, Rocio Aldana. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia. Universidad Tecnologica Nacional. Facultad Regional Haedo. Centro de Ingenieria de Recubrimientos Especiales y Nanoestructuras.; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Silveira Guimaraes, Francisco. Universidade de Sao Paulo; Brasil
Fil: Raisman Vozari, Rita. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia
Fil: Del Bel, Elaine. Universidade de Sao Paulo; Brasil
Fil: Michel, Patrick Pierre. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia
description To study the anti-inflammatory potential of the two synthetic cannabinoids 4′-F-CBD and HU-910, we used post-natal brain cultures of mouse microglial cells and astrocytes activated by reference inflammogens. We found that 4′-F-CBD and HU-910 efficiently curtailed the release of TNF-α, IL-6, and IL-1β in microglia and astrocytes activated by the bacterial Toll-Like Receptor (TLR)4 ligand LPS. Upon LPS challenge, 4′-F-CBD and HU-910 also prevented the activation of phenotypic activation markers specific to microglia and astrocytes, that is, Iba-1 and GFAP, respectively. In microglial cells, the two test compounds also efficiently restrained LPS-stimulated release of glutamate, a non-cytokine inflammation marker for these cells. The immunosuppressive effects of the two cannabinoid compounds were concentration-dependent and observable between 1 and 10 μM. These effects were not dependent on cannabinoid or cannabinoid-like receptors. Both 4′-F-CBD and HU-910 were also capable of restraining the inflammogenic activity of Pam3CSK4, a lipopeptide that activates TLR2, and of BzATP, a prototypic agonist of P2X7 purinergic receptors, suggesting that these two cannabinoids could exert immunosuppressive effects against a variety of inflammatory stimuli. Using LPS-stimulated microglia and astrocytes, we established that the immunosuppressive action of 4′-F-CBD and HU-910 resulted from the inhibition of ROS produced by NADPH oxidase and subsequent repression of NF-κB-dependent signaling events. Our results suggest that 4′-F-CBD and HU-910 may have therapeutic utility in pathological conditions where neuroinflammatory processes are prominent.
publishDate 2023
dc.date.none.fl_str_mv 2023-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/265488
dos Santos Pereira, Maurício; Maitan Santos, Bruna; Gimenez, Rocio Aldana; Silveira Guimaraes, Francisco; Raisman Vozari, Rita; et al.; The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes; Wiley-liss, div John Wiley & Sons Inc.; Glia; 72; 3; 11-2023; 529-545
0894-1491
CONICET Digital
CONICET
url http://hdl.handle.net/11336/265488
identifier_str_mv dos Santos Pereira, Maurício; Maitan Santos, Bruna; Gimenez, Rocio Aldana; Silveira Guimaraes, Francisco; Raisman Vozari, Rita; et al.; The two synthetic cannabinoid compounds 4′‐ F‐CBD and HU ‐910 efficiently restrain inflammatory responses of brain microglia and astrocytes; Wiley-liss, div John Wiley & Sons Inc.; Glia; 72; 3; 11-2023; 529-545
0894-1491
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/10.1002/glia.24489
info:eu-repo/semantics/altIdentifier/doi/10.1002/glia.24489
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley-liss, div John Wiley & Sons Inc.
publisher.none.fl_str_mv Wiley-liss, div John Wiley & Sons Inc.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268591253094400
score 13.13397

Publicaciones similares